Premium
Randomized phase II noncomparative trial of oral and intravenous doxifluridine plus levo‐leucovorin in untreated patients with advanced colorectal carcinoma
Author(s) -
Bajetta Emilio,
Di Bartolomeo Maria,
Somma Luisa,
Moreschi Monica,
Comella Giuseppe,
Turci Daniele,
Gebbia Vittorio,
Scanni Alberto,
Bordogna Gianni,
Stampino Corrado Gallo
Publication year - 1996
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/(sici)1097-0142(19961115)78:10<2087::aid-cncr8>3.0.co;2-l
Subject(s) - medicine , randomized controlled trial , bolus (digestion) , gastroenterology , fluorouracil , population , colorectal cancer , chemotherapy , surgery , cancer , environmental health
BACKGROUND Doxifluridine (5‐dFUR) is a fluoropyrimidine derivative that has been shown to be active on a variety of solid tumors. The clinical use of intravenous (i.v.) 5‐dFUR as a bolus injection or short term infusion has been limited because of its unpredictable severe neurotoxicity. Unlike fluorouracil (5‐FU), 5‐dFUR is effective when administered orally. METHODS This randomized, parallel‐group, Phase II trial of two schedules of 5‐dFUR was conducted between April 1993 and September 1994. A total of 130 previously untreated patients with locally advanced or metastatic colorectal carcinoma were randomized to receive oral levo‐leucovorin (l‐leucovorin) 25 mg/dose followed by oral 5‐dFUR 750 mg/m 2 twice daily for 4 days every 12 days (arm A) or i.v. l‐leucovorin 25 mg/dose followed by i.v. 5‐dFUR 3000 mg/m 2 for 5 days every 21 days (arm B). RESULTS The two treatment arms were well balanced in terms of age, sex, and disease extension. Metastases were present in more than 90% of the total population, with the liver being the most common site. A median of 7 oral courses (range, 1–15) and 5 intravenous courses (range, 1–9) were administered. Intent‐to‐treat analysis rate of the randomized patients revealed a response rate of 15% (95% confidence interval [CI], 7–26) in arm A and 41% (95% CI, 29–54) in arm B. However, 7 cases in arm A and 12 in arm B were inadequately treated, and the response rates, according to standard analysis, were respectively 17% (95% CI, 8–28) and 51% (95% CI, 37–65). The median time to treatment failure was 4 months (range, 1–23) and 7 months (range, 1–9), respectively, for the two groups; median survival was 11 months (range, 1–24) in both groups. National Cancer Institute Grade 3 and 4 diarrhea were observed in 25% of the orally treated patients and in 18% of those receiving i.v. treatment. Stomatitis was reported mainly in arm B (15%). Mild and moderate neurotoxicity was observed in 6% of the patients in both arms; no severe neurotoxicity was reported. CONCLUSIONS 5‐dFUR with l‐leucovorin, administered either orally or intravenously, produces response rates that are similar to those offered by the regimens containing 5‐FU that are usually used to treat advanced colorectal carcinoma. This study documents the good tolerance of the i.v. schedule administered as a 1‐hour infusion; furthermore, oral administration seems to be promising and feasible as a home treatment. Cancer 1996;78:2087‐93.